Haptoglobin(HP),an acute phase protein,can be found in mammalian animal plasma of human-being and other mammals.It plays important role in anti-infection,reparation of injured tissue,homeostasis.Different from other mammals,human-being have three different HP genotypes,HP1-1,HP2-2,HP2-1.Many studies have show that HP gene had been established as the susceptibility gene of diabetic cardiovascular disease.The review will introduce the structure and physiologic function of HP,summarize the basic and clinical researches about relationship between HP genotype and prevalence of cardiovascular diseases especially the cardiovascular complication of diabetic patients,prospect the prevention of cardiovascular complication of HP2-2 diabetic mellitus individual.
Objective To assess the influence of organic anion transporting polypeptide (OATP)1B1 A388G polymorphism on the pharmacokinetics of valsartan in healthy volunteers. Methods Pre-screening of OATP1B1 521TC was performed before this pharmacokinetic study. Twenty-three Chinese healthy male subjects who are OATP1B1 521TT wild-type homozygotes were selected to participate in this study. Fourteen were 388GG mutant homozygotes of OATP1B1,the others were carriers with at least one A allele (8 subjects had a genotype of 388AG and one was 388AA wild-type). Each was given a single oral dose of 80 mg valsartan. The plasma concentrations of valsartan were measured for up to 48 h by LC-MS. Results The pharmacokinetic parameters of valsartan showed a significantly difference between the two genotyped groups. The AUC0-48 and AUC0-∞ of valsartan were 51% higher in the 388AA-AG group than in the 388GG group[(24.8±11.1) μg·h·mL-1 vs (16.3±4.3) μg·h·mL-1,P0.05;(25.0±11.2) μg·h·mL-1 vs (16.5±4.4) μg·h·mL-1,P0.05]. The Cmax value was 39% higher in the 388AA-AG group than that in the 388GG group [(3.6±1.4) μg·mL-1 vs (2.6±0.9) μg·mL-1,P0.05]. The t1/2 and tmax values showed no difference between these groups. Conclusion The OATP1B1 A388G polymorphism may play an important role in the pharmacokinetics of valsartan in healthy Chinese males after the exclusion of impact of OATP1B1 T521C genetic polymorphism.
Objective To investigate aldehyde dehydrogenase 2(ALDH2) gene polymorphism on the metabolism of isosorbide-5-mononitrate (IS-5-MN) sustained-release tablets in healthy volunteers.Methods Apply PCR-RFLP to measure the genotypes of ALDH2 gene,subjects are divided into two groups according to their genotypes. Twenty-two healthy subjects are selected to take 60 mg IS-5-MN in single does,plasma concentration of IS-5-MN are measured by HPLC-MS in different specific time. Use pulse wave appearance to measure pulse wave analysis (PWA) parameters in blank situation and after taking medicine. Adverse effect was also recorded.Result The parameters of PWA,plasma concentration and adverse effect had no significant differences between the ALDH2*1/1and ALDH2*1/2 genotypes. But the PWA parameters had significant statistic differences in every single group. Conclusion ALDH2 gene polymorphism perhaps has no significant effect on the IS-5-MN metabolism.
脉搏波形分析(Pulse Wave Analysis)能够简单有效无创地评价大动脉功能及心脏负荷。在疾病的治疗与诊断、心血管药物的研究中发挥日益重要的作用。本文将就脉搏波形分析的图形、参数意义及临床应用作简要介绍。
Objective To investigate the effects of isosorbide-5- mononitrate on brachial blood pressure,central arterial pressure and arte- rial elasticity in healthy volunteers.Methods A single oral dose 60 mg of isosorbide-5-mononitrate (IS-5-MN) was given to 18 healthy male volunteers in a self-controlled study.The difference in blood pres- sure,pulse wave and heart rate of the dosing day were compared to that of the day before in 16 hours.Results After a single IS-5-MN admin- istration,augment index (AI) and central artery pulse pressure were dropped significantly.Brachial blood pressure,central systolic blood pressure,central diastolic blood pressure and heart rate had no apparent change.Conclusion IS-5-MN improved the artery compliance and reduced central artery pulse pressure in healthy male volunteers.
AIM: To investigate the effects of polymorphisms of aldehyde dehydrogenase 2 gene(ALDH2)at positions Glu504Lys on pharmacokinetic(PK) characteristics of isosorbide-5-mononitrate (IS-5-MN) in Chinese healthy volunteers. METHODS:Among 45 persons, twenty-two healthy male volunteers were selected and orally taken 60 mg IS-5-MN.An HPLC-MS method was applied to analyze IS-5-MN plasma concentration.ALDH2 genotype was determined by PCR-RFLP. Pharmacokinetic analysis was performed to assess the effects of the genotype on IS-5-MN pharmacokinetics. RESULTS: In these 22 volunteers,13 homozygous GG and 9 heterozygous GA genotypes for ALDH2 at positions of Glu504Lys were detected by PCR-RFLP. IS-5-MN plasma concentration, AUC0-t, Cmax and tmax did not show significant statistical difference (P0.05) in the two groups. CONCLUSION: The polymorphisms of ALDH2 gene at positions of Glu504Lys could not influence the pharmacokinetics of IS-5-MN in the research.